Diabetes Treatment
Medical treatment of several illnesses requires continuous drug infusion into various body compartments, such as subcutaneous and intra-venous injections. Diabetes mellitus (DM) patients, for example, require the administration of varying amounts of insulin throughout the day to control their blood glucose levels. In recent years, ambulatory portable insulin infusion pumps have emerged as a superior alternative to multiple daily syringe injections of insulin, initially for Type 1 diabetes patients and consecutively for Type 2 diabetes patients. These pumps, which deliver insulin at a continuous basal rate as well as in bolus volumes, were developed to liberate patients from repeated self-administered injections, and allow them to maintain a near-normal daily routine. Both basal and bolus volumes must be delivered in precise doses, according to individual prescription, since an overdose or under-dose of insulin could be fatal.
Generations of Insulin Pumps and Continuous Glucose Sensors
The first generation of portable insulin pumps refers to a “pager like” device with a reservoir included within a housing and long tubing is required to deliver insulin from the reservoir to the infusion site. Examples of such devices are disclosed in U.S. Pat. Nos. 6,248,093 and 7,390,314. These devices are usually heavy and bulky and the tubing substantially disturbs daily activity.
To avoid the limitations of first generation infusion pumps, an additional concept was proposed, which was implemented in second generation pumps. The additional concept concerns a remote controlled skin adherable device having a bottom surface adapted to be in contact with the patient's skin. The reservoir is contained within a housing and filled using an additional syringe. This paradigm was discussed, for example, in U.S. Pat. Nos. 5,957,895, 6,589,229, 6,740,059, 6,723,072, and 6,485,461. These second generation skin adherable devices still have several drawbacks, the most significant being that the entire device should be disposed of every 2-3 days (due to insertion site infections and reduced insulin absorption) including all the expensive components (electronics, driving mechanism, etc.).
Third generation skin-securable devices were devised to avoid the cost issues of the second generation devices and to extend patient customization. An example of such a device is described in U.S. Patent Application Publication No. 2007-0106218 and in International Patent Application Publication No. WO/2007/052277. This third generation device contains a remote control unit and a skin-securable (e.g., adherable) patch unit that include two parts: (1) a reusable part containing the electronics, at least a portion of the driving mechanism and other relatively expensive components, and (2) a disposable part containing the reservoir. A skin-securable fluid (e.g., insulin) delivery device is also disclosed in U.S. patent application Ser. No. 11/989,681 and in International Patent Application Publication No. WO/2008/012817, the disclosures of which are incorporated herein by reference in their entireties.
A fourth generation infusion device was devised as a dispensing unit that can be disconnected and reconnected to a skin-adherable cradle unit, as disclosed, for example, in U.S. Patent Application Publication No. 2008-0215035 and in International Patent Application Publication No. WO/2008/078318. Such skin-securable dispensing units can be operated using a remote control and/or a user interface (e.g., a button-based interface) provided on a housing of the dispensing unit, as disclosed, for example, in International Patent Application Publication No. WO/2009/013736, filed Jul. 20, 2008, claiming priority to U.S. Provisional Patent Application No. 60/961,527, and entitled “Manually Operable Portable Infusion Device”, and in International Patent Application Publication No. WO/2009/016636, filed Jul. 31, 2008, claiming priority to U.S. Provisional Application Ser. Nos. 60/963,148 and 61/004,019, and entitled “Portable Infusion Device Provided with Means for Monitoring and Controlling Fluid Delivery”, the disclosures of which are incorporated herein by reference in their entireties.
The third and fourth generation dispensing patches can be incorporated with an analyte (i.e. glucose) sensing apparatus enabling continuous readings of analyte levels. Fluid dispensing can be done automatically according to analyte sensing (closed loop system) or semi automatic if the user wishes to control delivery (open loop system). Such dual function sensing and dispensing devices are disclosed, for example, in U.S. Patent Application Publication No. 2007-0191702, the disclosure of which is incorporated herein by reference in its entirety.
Pump Gears and Transmission Error
The pumping mechanism employed in most insulin pumps is a “syringe-like mechanism”, known also as a positive displacement piston pump. In such a pump, a plunger (piston) moves (i.e., slides) within a cylindrical shaped barrel (reservoir), pushing the contents (i.e., drug) out, typically, through a small opening at the end of the reservoir/syringe. The plunger is pushed forward by a drive-screw (plunger rod) that can be integral, rigidly connected, or articulated with the plunger head (piston). The driving mechanism typically consists of a motor and a transmission gear system, which is used to linearly displace the drive-screw either by rotation of the drive-screw, rotation of a drive nut, or rotation of a drive pinion over a rack that serves as a drive-screw (a rack is a toothed bar or rod. Torque is converted to linear force by meshing a rack with a pinion: the pinion turns; the rack moves in a straight line). The transmission gear system is used for reduction of motor revolutions and/or for changing the rotation axis by 90 or 180 degrees, for example.
Typically, the pump's transmission gear system consists of two or more parallel shaft gears (e.g., single stage reduction), comprising two metal cogwheels, integrated with a tooth mesh and both cogwheel shafts are parallel mounted on a metal chassis (gear casing).
Transmission error (hereinafter referred to also as “TE”) is defined as the difference between the actual position of the output gear and the position it would occupy if the gear drive were perfectly conjugated. The equation for TE is expressed as:
  TE  =            θ      2        -                  (                              Z            1                                Z            2                          )            ⁢              θ        1            Where Z1 is the number of teeth of the input gear, Z2 is the number of teeth of the output gear and θ1 and θ2 denote the angular position of the input and output gears in radians, respectively. Essentially, TE is the difference between the actual position of the output shaft of a gear drive and the position that the output shaft of the gear drive would have if the gear drive were perfect, without errors or deflections. The main contributors to transmission error are geometrical errors in alignment (e.g., due to assembly errors/tolerances), tooth profile (e.g., due to manufacturing imperfections/tolerances), elastic deformation of local contacts, and the deflection of the gear shafts and casing due to the transmitted load through and transverse to the gear rotation axis. Depending on its cause, the frequency of the transmission error may be high (i.e., >1 per cycle of the output shaft), or it may be substantially equal to the frequency of the output shaft's rotation (i.e., =1 per cycle of the output shaft). The magnitude of this one per cycle error may depend on load and it may thus be classified as loaded TE.
A consequence of TE existing in transmission gear systems of insulin pumps is inaccuracy in drug delivery. Insulin pumps should deliver basal doses at a very low rate along the entire day with high precision (e.g., 0.05 U/h that is 5 mm3/h in case of 100 U/ml rapid acting insulin). Typically, the existence of TE introduces a “sine like” wave to the expected drug delivery linear curve with fluctuations that can substantially affect insulin delivery accuracy and threaten the life of the diabetes patient.
It is understood that TE is may be minimized in gear systems of 1st generation pumps by making gears, gear casings, and bearings robust (e.g., relatively large components, metal components). Consequently these “pager like” pumps are undesirably heavy, bulky, and expensive.
The design goal of skin securable 2nd, 3rd, and 4th generation pumps, however, is that they be small and lightweight, with minimal components and assembly costs. Consequently, the gears, gear casing, and bearings for these pumps are configured to be miniature and lightweight and therefore, they are typically made of plastic (i.e., polycarbonate, polypropylene, etc.). These plastic parts should maintain metal parts' requirements and avoid (or minimize) transmission error. However, plastic parts, especially miniature plastic parts, are typically more subject to manufacturing (e.g., injection molding) and assembly imperfections than metal parts, and are also typically more subject to deformations caused by forces/load applied during routine operation of the pump, all of which are likely to result in transmission error. Transmission error may further be aggravated in 3rd and 4th generation two-part skin securable pumps because the interface between the drive-screw (piston rod) and gear is achieved during connection of the two parts by the user, thus increasing the risk of component misalignment, for example.
Thus, it is desirable to provide a skin securable drug dispensing patch unit which is miniature, discreet, economical for the users and highly cost effective. The patch unit includes a driving mechanism comprising a motor and a gear system with minimized transmission error, for delivering fluids at a high accuracy rate.
It is also desirable to provide a skin securable drug dispensing patch unit that includes two parts, e.g., a reusable part and a disposable part. The disposable part (“DP”) includes a reservoir and a slidable plunger. The reusable part (“RP”) includes electronics, and at least a portion of a driving mechanism including a motor and a gear system with minimized transmission error, for delivering fluids at a high accuracy rate.